The first part of the proposed work is the development and validation of an intervertebral disc explant culture system. The second part of the proposed work is experimental studies investigating the effects of mechanical compression of the disc explants on the metabolic activity of the disc cells. Elucidation of the loading parameters that are beneficial and detrimental to disc health is necessary for the development of appropriate preventative measures and treatment therapies for low back pain and for the design of tissue engineered replacements of the degenerate disc. The establishment of a reliable in vitro culture system for intervertebral disc implants is an important step in furthering our understanding of the effects of mechanical loading on disc metabolism. The development of an in vitro explant culture system would provide for compromise between the in vivo and isolated cell systems, allowing for controlled evaluation of the effects of mechanical loading on disc cell metabolism. The initial experimental work that will be conducted under this proposed project will lay the groundwork for future in vitro and in vivo studies on intervertebral disc mechanobiology. [unreadable] [unreadable]